title: Progress of molecular targeted therapies for advanced renal cell carcinoma.
abstract: Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α 5 β 1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3'-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents.
authors.affiliation: Department of Clinical and Specialist Sciences, Urology, Polytechnic University of the Marche Region, AOU Ospedali Riuniti Umberto I-GM Lancisi and G Salesi, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Conti
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Consuelo
authors.initials: C
authors.lastname: Amantini
authors.forename: Luciano
authors.initials: L
authors.lastname: Burattini
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Muzzonigro
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D011804:Quinolines / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics*; D007211:Indoles
chemical_list: D010671:Phenylurea Compounds; D011799:Quinazolines; D011804:Quinolines; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human; C553176:tivozanib; C500926:cediranib; D007211:Indoles